Cholinergic stimulation with pyridostigmine prevents the impairment in ventricular function during mental stress in coronary artery disease patients

Pyridostigmine Restores Cardiac Autonomic Balance after Small Myocardial Infarction in Mice

“…In humans, the acute administration of PYR produced bradycardia [26], increased the ventricular refractory period and displayed a potential anti-arrhythmic effect at higher HR [27]. In patients with coronary artery disease and heart failure, PYR prevented the myocardial dysfunction induced by mental stress [19], ameliorated the autonomic and hemodynamic profile during exercise [28]–[30], improved the HR recovery after exercise [31] and reduced ventricular arrhythmia density [25]. Moreover, our laboratory has observed a protective effect of PYR on cardiac autonomic control, intrinsic HR, baroreflex sensitivity, and cardiac function four [20] and six weeks [21] after the onset of heart failure in rats.…”

“…Previous studies have demonstrated that short-term administration of PYR may be potentially useful for cardiovascular protection because it shifts the autonomic balance toward parasympathetic predominance, resulting in beneficial effects on markers of cardiovascular risk and dysfunction [19]–[22]. PYR increased HR variability in normal rats [23], healthy humans [24] and patients with heart failure [25].…”

Acute electrophysiologic consequences of pyridostigmine inhibition of cholinesterase in humans

“…Albeit exhibiting promising effects, edrophonium needs to be administered intravenously, precluding its prescription for regular use. Therefore, pyridostigmine, which can be administered orally and causes a dose-dependent vagomimetic effect with few side effects (13)(14)(15)(16)(17)(18)(19), is a preferable candidate for the treatment of impaired parasympathetic modulation in heart disease. As a drug that elicits a parasympathetic effect, pyridostigmine was expected to cause bradycardia in the present study.…”

“…In addition, it has been shown to counteract the adverse anti-cholinergic effects of disopyramide, such as decreased baseline saliva and tear production (12). We have previously shown that short-term administration of pyridostigmine may be also potentially useful for cardiovascular protection since in healthy individuals and patients with cardiovascular diseases it results in beneficial effects on markers of cardiovascular risk and dysfunction (8,(13)(14)(15)(16)(17)(18)(19).…”

“…In patients with coronary artery disease, pyridostigmine improves the autonomic and hemodynamic responses to exercise (13,14,19), prevents the myocardial dysfunction induced by mental stress (16), and reduces QTc dispersion (18). In a randomized, crossover, placebo-controlled, and double-blind study, pyridostigmine administration increased heart rate variability and reduced ventricular arrhythmia density in patients with heart failure (17), an effect mediated, at least in part, by stimulation of the endogenous nitric oxide pathway (20).…”